ABSTRACT
A study was conducted on the activity exerted by prolonged dietary supplementation with progressive amounts of retinoids on cell-mediated immune responses and the growth of transplantable tumors in mice. A few groups of BALB/c mice received 0 (group C), 50 (group A 50), 200 (group A 200), 500 (group A 500), and 1,000 (group A 1000) IU retinol palmitate/mouse/day in drinking water for 150 days. At progressive intervals mice from each group were tested for proliferative responses to concanavalin A (Con A), Escherichia coli lipopolysaccharide, interleukin-2, and interferon-gamma release to Con A. Ten mice from each group were also challenged with the 90-100% tumor-inducing dose of 3 distinct transplantable tumors. At the end of the experiment the principal organs were histologically examined, and the accumulation of vitamin A was evaluated. In groups A 200, A 500, and A 1000, an increase in the proliferative responses and production of lymphokines as compared to those in group C occurred after 60-90 days, but vanished after 150 days. The takes of the 3 tumors were impaired when the challenges were performed on days 75 and 150. This enhancement of distinct functions of cellular reactivity and resistance to transplantable tumors showed a linear relationship with the amount of supplemental retinol palmitate for the first 60-90 days. After 150 days, however, these enhancement effects vanished or tended to decrease.
Subject(s)
Immunity, Cellular/drug effects , Neoplasms, Experimental/pathology , Retinoids/administration & dosage , Animals , Concanavalin A/pharmacology , Diet , Diterpenes , Dose-Response Relationship, Drug , Female , Fibrosarcoma/pathology , Interferon-gamma/biosynthesis , Interleukin-2/biosynthesis , Lipopolysaccharides/pharmacology , Lymphocyte Activation/drug effects , Mammary Neoplasms, Experimental/pathology , Mice , Mice, Inbred BALB C , Neoplasm Transplantation , Neoplasms, Experimental/immunology , Retinoids/pharmacology , Retinyl Esters , Vitamin A/analogs & derivatives , Vitamin A/pharmacologyABSTRACT
Groups of BALB/C mice received a diet supplement of 0 (group C), 200 (group A 200), 500 (group A 500), and 1,000 (group A 1,000) IU retinol palmitate (RP)/mouse/day in drinking water for 450 days. At progressive time intervals, mice from each group were tested for natural killer (NK) activity and for the percentage of large granular lymphocytes (LGL) in the spleen. In groups A 200, A 500 and A 1,000, a dose-dependent increase in NK activity was evident 50 days after the beginning of RP supplementation and was accompanied by a parallel increase of LGL number in the spleen. In group A 1,000, the increase of spontaneous or Poly I:C-induced cytotoxicity persisted until day 160. By contrast, inhibition of Poly I:C-induced NK cytotoxicity was found in this group at day 450.
Subject(s)
Immunity, Innate/drug effects , Killer Cells, Natural/immunology , Vitamin A/analogs & derivatives , Age Factors , Animals , Cytotoxicity, Immunologic/drug effects , Diterpenes , Dose-Response Relationship, Drug , Mice , Retinyl Esters , Spleen/cytology , Spleen/immunology , Time Factors , Vitamin A/pharmacologyABSTRACT
Malondialdehyde reacts readily with amino acids to form adducts containing vinylogous amidine linkages. Crosslinking reactions between nucleic acid bases and amino acids induced by malondialdehyde also have been investigated. The physical data obtained for the adducts provide structural information on the possible mode of crosslinking of proteins and nucleic acids induced by this lipid metabolite.
Subject(s)
Lipid Peroxides/metabolism , Malonates , Malondialdehyde , Chemical Phenomena , Chemistry , Gas Chromatography-Mass Spectrometry , Magnetic Resonance Spectroscopy , SpectrophotometryABSTRACT
The role of vitamin A and its analogs (retinoids) in the prevention and therapy of neoplastic diseases is discussed. Epidemiological data showing a relationship between vitamin A deficiency and increased frequency of tumors in man and animals are examined and the experimental models demonstrating the protective action of retinoids in the respect of both spontaneous and induced neoplasias of animals are reviewed. Among the possible mechanisms responsible of the antineoplastic activity, the immunopotentiating effect is underlined. Some toxicological aspects of retinoids administration and the consequent application of the experimental results in human medicine are finally discussed.
Subject(s)
Neoplasms/prevention & control , Vitamin A/therapeutic use , Animals , Antibody Formation/drug effects , Cell Transformation, Neoplastic/drug effects , Graft Rejection/drug effects , Humans , Lung Neoplasms/etiology , Mice , Retinoids/therapeutic use , Retinoids/toxicity , Retinol-Binding Proteins/metabolism , Vitamin A Deficiency/complicationsABSTRACT
A novel structural analogue of cyclic AMP has been synthesized. This compound has been found to activate protein kinase from skeletal muscle (Ka 5.0 microM). It is virtually resistant to degradation by beef heart cAMP phosphodiesterase. It is an inhibitor of this enzyme with an [I]50 of 47.0 microM. The proliferation of cancer cells (HT-29) is inhibited by this compound. It represents the first example of a 2',3'-cyclic nucleotide with marked biological activity.
